Anti-Gastritis and Anti-Ulcer Agent Containing Momordicae Semen Extract and Momordica Saponin I Isolated From the Same

ABSTRACT

The present invention relates to a  Momordicae semen  extract effective in the prevention and treatment of gastritis or gastric ulcer and momordica saponin I isolated therefrom. The  Momordicae semen  extract and the momordica saponin I isolated therefrom is effective in the prevention and treatment of gastritis or gastric ulcer since they prevent the damage of the gastric mucosa caused by alcohols and inhibit the secretion of gastric acid.

TECHNICAL FIELD

The present invention relates to a Momordicae semen extract effective inthe prevention and treatment of gastritis or gastric ulcer and momordicasaponin I isolated therefrom.

BACKGROUND ART

The gastric mucosal layer which protects the stomach can be easilydamaged by various factors. Typical factors of such include gastricacid, alcohols, non-steroidal anti-inflammatory drugs (NSAID) such asaspirin, bacteria such as Helicobacter pylori [Suzuki. M. and S. Miura,Nippon Rinsho, 15(12), 3154-3158, 1993], disturbance of microcirculationof gastric mucosa and hypotension caused by stress [Tadaoki Mizuno,Yokohama Med. Bull., 38(3,4) , 87-97, 1987], etc. When the mucosal layeris damaged by the above factors, there occurs inflammation which isaccompanied by flare, hemorrhage and edema. In severe cases, this maylead to damage in the submucosa and the muscle layer, called gastriculcer. Further, the duodenum which is in direct contact with the stomachmay get inflammation or ulcer because of the exposure to similarfactors.

For the treatment of the inflammation and ulcer of the stomach and theduodenum caused by these factors, it is essential to develop a drugeffective in inhibiting the secretion of gastric acid, inhibiting theproliferation of Helicobacter pylori, stimulating the secretion ofmucus, promoting the regeneration of epithelial cells, fighting againstinflammation, etc. At present, the most typical treatments for gastritisand gastric ulcer are H2 antagonists and proton pump inhibitorseffective in inhibiting the secretion of gastric acid. These drugs areshown to have superior clinical effect [J. Int. Med. Res. 17(suppl.) 9A,1989; Meth. Find. Exp. Clin. Pharmacol. 11(suppl. 1) 87, 1989; N. Eng.J. Med. 323: 1672, 1990]. However, these gastric acid secretioninhibitors have a drawback that the condition recurs when theadministration of the drugs is stopped [Drug Intell. Clin. Pharm. 21:493, 1987, Gut 30: 449, 1989 Yale J. Biol. Med. 65: 649, 1992].

The mucosal protectant, which promotes the regeneration of the mucosaltissue to ensure protection against the re-attack of gastritis inducingfactors to reduce the recurrence of gastritis, is an important componentof the gastritis treatment. Currently, such drugs as rebamipide,sofalcone, etc., are available as a gastric mucosal protectant. However,they should be taken in large amount for a long period of time due tothe rather slow actions of these drugs, and thus there is a need for thedevelopment of improved drugs.

One of the most commonly used methods of assessing the efficiency ofgastritis treatment using an animal model is to introduce damage on thegastric mucosa by using non-steroidal anti-inflammatory drugs (NSAID) orethanol, and observe the rate of recovery. Through these animal modeltests, various herbal extracts have been reported as candidates for thetreatment of gastritis. In particular, the extract of Artemisia Sppshaving superior effect in treating gastritis has been applied for apatent [Korean Patent Application No. 10-1995-0021957] and developed asa commercial drug named Stillen® by Dong-A Pharmaceutical.

The Momordicae semen used in the present invention is a ripe seed ofMomordica, a perennial vine which grows widely in southern China andVietnam. Fruits harvested between September and November are cut in halfand the seeds are collected when they are half dry. Or, the fruits areput into jars and the seeds are taken when the rinds become rotten.Momordicae semen is known to have good anti-inflammatory activity and beeffective against rheumatic pain, muscular spasm, etc. At present, theMomordicae semen extract is known to contain sterol, oleanolic acid,momordic acid, etc.

The present inventors have made extensive efforts to develop a treatmentfor gastritis. In doing so, they discovered that the Momordicae semenextract and momordica saponin I isolated therefrom reduce the damage ofthe gastric mucosa induced by diclofenac and alcohols in rats. They alsodiscovered that the administration of Momordicae semen extract andmomordica saponin reduces the acidity in the stomach.

Accordingly, an object of the present invention is to provide a drug forthe prevention and treatment of gastritis or gastric ulcer comprisingMomordicae semen extract or momordica saponin I as an active ingredientwhich is superior in protecting the gastric mucosa and inhibitinggastric acid.

DISCLOSURE OF THE INVENTION

The present invention relates to a drug for the prevention and treatmentof gastritis or gastric ulcer comprising Momordicae semen extract as anactive ingredient.

The present invention also relates to a drug for the prevention andtreatment of gastritis or gastric ulcer comprising momordica saponin I,which is represented by the following formula (1), as an activeingredient.

Hereunder is given a more detailed description of the present invention.

The present invention relates to a drug comprising Momordicae semenextract and momordica saponin I isolated therefrom, which are effectivein the prevention and treatment of gastritis or gastric ulcer with goodinhibition activity against the damage of gastric mucosa caused byalcohols and non-steroidal anti-inflammatory drugs (NSAID) such asdiclofenac and good inhibition activity against the secretion of gastricacid.

The Momordicae semen extract of the present invention is obtained byextracting the herb Momordicae semen 3-10 weight equivalents of water oralcohol solution, according to the common method used to extract herbs.Preferably, said alcohol is C₁-C₆ alcohol, more preferably, methanol,ethanol, butanol, etc.

The Momordicae semen extract is lyophilized to obtain the extract inpowder form. With good activity for the prevention and treatment of thedamage of gastric mucosa induced by diclofenac and alcohols, thisextract is expected to be very useful as a drug for the prevention andtreatment of gastritis or gastric ulcer.

In addition, the momordica saponin I of the present invention can beefficiently isolated from Momordicae semen by the common method usingpolar solvent. For the polar solvent, distilled water or alcoholsolution may be used. Preferably, the alcohol is a C₁-C₆ alcohol, morepreferably, methanol, ethanol, butanol, etc.

Particularly, column chromatography may be performed to obtain momordicasaponin I with better purity. More specifically, a chromatography columnis prepared using octadecylsilylated silica resin, etc. and suchadequate solvent as 70% (v/v) aqueous methanol solution, etc. is used toselectively separate the fraction with a high saponin concentration.

With superior effect of preventing and treating the damage of gastricmucosa induced by alcohol or diclofenac and good effect of preventingthe secretion of gastric acid, momordica saponin I is a good candidatefor the drug for the prevention and treatment of gastritis or gastriculcer.

The Momordicae semen extract or momordica saponin I of the presentinvention is prepared into tablet or capsule by the common method. Incase of tablets, one having activity for the prevention and treatment ofgastritis or gastric ulcer can be prepared using a matrix comprisinglactose, microcrystalline cellulose, magnesium stearate, etc., and anactive ingredient, or the Momordicae semen extract or momordica saponinI of the present invention, at a proportion of 2-10 to 1.

The active ingredient may be used either in itself or after mixing witha pharmaceutically acceptable carrier, a forming agent, a diluent toobtain the formulation in the form of powder, granules, capsules, etc.The dosage of Momordicae semen extract or momordica saponin I of thepresent invention may vary depending on absorption rate, body weight,age, sex, physical conditions, diet, administration time, type ofadministration, severity of disease, and the like. As a general rule,about 0.1-10 mg per 1 kg of body weight is preferable for the Momordicaesemen extract and about 0.05-1 mg per 1 kg of body weight is preferablefor the momordica saponin I. The drug in the unit dosage form may beadministered through a customized medication plan or several times withpredetermined intervals, depending on the decision of an expert whomonitors the administration or on the demand of the patients.

BEST MODE FOR CARRYING OUT THE INVENTION

Practical and presently preferred embodiments of the present inventionare illustrative as shown in the following examples. However, it will beappreciated that those skilled in the art may, in consideration of thisdisclosure, make modifications and improvements within the spirit andscope of the present invention.

Preparative Example 1 Preparation of Momordicae semen Extract

To 1 kg (dry weight) of Momordicae semen purchased from at the herbmarket was added 5 L of 50% aqueous ethanol solution. Extraction wasperformed for 4 hours while maintaining the temperature at 80° C. Thisprocedure was repeated twice to obtain the herb extract. The extract wasfiltered and concentrated under reduced pressure at 60° C. using arotary evaporator. Then, after completely removing the solvent in avacuum oven, 21 g of ethanol extract in powder form was obtained.

Preparative Example 2 Preparation of Extract Containing MomordicaSaponin I

1 kg (dry weight) of Momordicae semen purchased from at the herb marketwas crushed and 5 L of 10% aqueous ethanol solution was added.Extraction was performed for 3 hours in a water bath kept at 80° C. Thisprocedure was repeated twice. The extract was filtered and concentratedunder reduced pressure at 60° C. using a rotary evaporator. Then, aftercompletely removing the solvent in a vacuum oven, 35-45 g of extractcontaining momordica saponin I was obtained in powder form.

Preparative Example 3 Preparation of Momordica Saponin I Fraction

Momordica saponin I was effectively isolated from the extract preparedin Preparative Example 2 through precipitation using organic solvent(acetone). 10 g of the extract prepared in Preparative Example 2 wasdissolved in 100 mL of purified water and 100 mL of acetone was added toobtain 50% (v/v) aqueous acetone solution. Precipitate was filtered offand 400 mL of acetone was further added to the filtrate to obtain 80%(v/v) aqueous acetone solution. The newly formed precipitate wasseparated using a filter paper and dried.

Preparative Example 4 Preparation of Momordica Saponin I Fraction

Column chromatography was performed on the extract prepared inPreparative Example 2 or the fraction obtained in Preparative Example 3using octadecylsilylated silica resin (YMC*GEL ODS-A 12 nm, S-150 m).The amount of the resin was 250 g, or 25 times the weight of the extractor the fraction. Each of 10% (v/v) and 40% (v/v) aqueous methanolsolution, which is 2-3 times the volume of the resin, was flown and then70% (v/v) aqueous methanol solution, which is 2-3 times the volume ofthe resin, was flown. The resultant elution fraction was concentratedunder reduced pressure and the solvent was completely removed in avacuum oven.

Preparative Example 5 Isolation of Momordica Saponin I

Momordica saponin I was isolated from the 70% (v/v) aqueous methanolsolution fraction of Preparative Example 4. High performance liquidchromatography was performed using a mixed solvent of acetonitrile andwater (29:71, 0.1% trifluoroacetic acid). Elution was performed at arate of 9.5 mL/min and the saponin peak was taken at about 45 minutes.This fraction was concentrated under reduced pressure and the solventwas completely removed in a vacuum oven. YMC J‘Sphere ODS-H80 column wasused and the measurement was made at 210 nm.

Mass spectroscopy and NMR spectroscopy data were compared with thosepresented in the literature [Iwamoto, Okabe, Yamauchi, Tanaka, Rokutani,Hara, Mihashi, Higuchi. Studies on the constituents of Momordicacochinchinensis Spreng. I. Isolation and characterization of the seedsaponins, momordica saponin I and II. Chemical & Pharmaceutical Bulletin1985, 33(2):464-478]. The data coincided with those of momordica saponinI(3-O-β-D-galactopyranosyl(1->2)-[α-L-rhamnopyranosyl(1->3)]-β-D-glucuronopyranosido-28-O-β-D-xylopyranosyl(1->3)-β-D-glucopyranosyl(1->3)-[β-D-xylopyranosyl(1->4)]-α-L-rhamnopyranosyl(1->2)-β-D-fucopyranosylgypsogenin),which is known to be present in Momordicae semen.

Molecular weight: 1673.77

Melting point: 241-244° C.

Optical rotation: [α]19 D=−14.8° (C 0.7, MeOH:H₂O=1:2)

The contents of momordica saponin I in the extract or the fraction ofPreparative Examples 2 to 4 are given in Table 1 below.

TABLE 1 Preparative Preparative Preparative Category Example 2 Example 3Example 4 Contents of momordica 7-14 13-25 40-50 saponin I (%)

Example 1 Protective Effect of Momordicae semen Extract Against theStomach Damage Induced by Alcohol

A rat model test was performed using 100% ethanol as stomach damageinducing factor to evaluate the protective effect of the Momordicaesemen extract for gastric mucosa. The Momordicae semen extract ofPreparative Example 1 was dissolved in 0.5% aqueous carboxymethylcellulose solution to 10 mg/mL and was used as a test drug. Stillen(artemisia extract, Dong-A Pharmaceutical) and Mucosta (rebamipide,Korea Otsuka Pharmaceuticals) dissolved in 0.5% aqueous carboxymethylcellulose solution to 10 mg/mL were used as control drugs.

Seven-week-old specific pathogen free (SPF) male Sprague-Dawley ratswere purchased from Charles River. After 1 week of adaptation, healthyrats with a weight of 220-225 g were selected for the test. Five ratsper each group were fasted for 18 hours with drinking water freelyavailable. The Momordicae semen extract and the control drugs Stillenand Mucosta were administered at a dosage of 100 mg/kg. After 1 hour,1.5 mL of 100% ethanol was orally administered. 6 hours later, the ratswere anesthetized with ether and the stomach was taken out in order toevaluate the drug's effect of preventing the stomach damage. The stomachwas cut open along the greater curvature and was observed with eyes. Thedamage of the stomach was categorized into flare, congestion,hemorrhage, inflammation and edema. The severity of the damage wasevaluated with points ranging from 0 to 3.

TABLE 2 Damage of gastric mucosa (gastric mucosa damage index) CategoryFlare Hyperemia Bleeding Erosion Edema Total Water 1.8 ± 0.2 1.6 ± 0.22.4 ± 0.4 1.8 ± 0.4 1.8 ± 0.4 9.4 ± 1.3 Stillen 1.8 ± 0.2 1.4 ± 0.2 1.0± 0.5 1.2 ± 0.2 1.2 ± 0.4 7.7 ± 1.2 Mucosta 1.3 ± 0.2 1.3 ± 0.4 1.5 ±0.2 1.8 ± 0.2 1.3 ± 0.2 8.1 ± 0.8 Momordicae 1.0 ± 0.3 1.0 ± 0.3 0.8 ±0.2 1.5 ± 0.2 1.0 ± 0.3 6.4 ± 1.3 semen extract

As seen in Table 2, the Momordicae semen extract had superior effect ofpreventing the damage of gastric mucosa induced by alcohol.

Example 2 Protective Effect of Momordica Saponin I Against the StomachDamage Induced by Alcohol

A rat model test was performed using 100% ethanol as stomach damageinducing factor to evaluate the protective effect of momordica saponin Ifor gastric mucosa. The momordica saponin I isolated in PreparativeExample 5 was dissolved in 0.5% aqueous carboxymethyl cellulose solutionto 2 mg/mL and was used as a test drug. Mucosta (rebamipide, KoreaOtsuka Pharmaceuticals) dissolved in 0.5% aqueous carboxymethylcellulose solution to 10 mg/mL was used as control drug.

Seven-week-old specific pathogen free (SPF) male Sprague-Dawley ratswere purchased from Charles River. After 1 week of adaptation, healthyrats with a weight of 220-225 g were selected for the test. Five ratsper each group were fasted for 18 hours with drinking water freelyavailable. Momordica saponin I were administered at a dosage of 20 mg/kgand the control drug Mucosta were administered at a dosage of 100 mg/kg.After 30 minutes, 1.5 mL of 100% ethanol was orally administered. 3hours later, the rats were anesthetized with ether and the stomach wastaken out in order to evaluate the drug's effect of preventing thestomach damage. The stomach was cut open along the greater curvature andwas observed with eyes. The damage of the stomach was classified intoflare, congestion, hemorrhage, inflammation and edema. The severity ofthe damage was evaluated with points ranging from 0 to 3 (the higher thepoint, the severer the damage.).

TABLE 3 Damage of gastric mucosa (gastric mucosa damage index ± standarddeviation) Category Flare Hyperemia Bleeding Erosion Edema Total Water1.9 ± 0.3 1.5 ± 0.3 2.5 ± 0.5 0.7 ± 0.2 1.3 ± 0.2 7.9 ± 1.5 Mucosta 1.2± 0.2 1.4 ± 0.2 1.4 ± 0.2 0.9 ± 0.3 1.2 ± 0.3 6.1 ± 1.2 Momordica 1.1 ±0.2 0.9 ± 0.3 0.9 ± 0.2 0.5 ± 0.1   1 ± 0.3 4.4 ± 1.1 saponin I

As seen in Table 3, momordica saponin I had superior effect ofpreventing the damage of gastric mucosa induced by alcohol.

Example 3 Healing Effect of Momordicae semen Extract on the StomachDamage Induced by Diclofenac

A rat model test was performed using diclofenac, a representativenon-steroidal anti-inflammatory drug (NSAID), as stomach damage inducingfactor to evaluate the effect of the Momordicae semen extract of Example1 for treating gastritis. The Momordicae semen extract was dissolved in0.5% aqueous carboxymethyl cellulose solution to 10 mg/mL and was usedas a test drug. Stillen (artemisia extract, Dong-A Pharmaceutical) andMucosta (rebamipide, Korea Otsuka Pharmaceuticals) dissolved in 0.5%aqueous carboxymethyl cellulose solution to 10 mg/mL were used ascontrol drugs.

Seven-week-old specific pathogen free (SPF) male Sprague-Dawley ratswere purchased from Charles River. After 1 week of adaptation, healthyrats with a weight of 220-225 g were selected for the test. Five ratsper each group were fasted for 18 hours with drinking water freelyavailable and diclofenac was orally administered at a dosage of 40mg/kg. After 6 hours of stomach damage inducement, the Momordicae semenextract and the control drugs Stillen and Mucosta were administered at adosage of 100 mg/kg. 18 hours later, the rats were anesthetized withether and the stomach was taken out in order to evaluate the drug'seffect of treating gastritis. The stomach was cut open along the greatercurvature and was observed with eyes. The damage of the stomach wasclassified into flare, congestion, hemorrhage, inflammation and edema.The severity of the damage was evaluated with points ranging from 0 to3.

TABLE 4 Damage of gastric mucosa (gastric mucosa damage index) CategoryFlare Hyperemia Bleeding Erosion Edema Total Water 2.6 ± 0.2 2.4 ± 0.42.6 ± 0.2 2.6 ± 0.2 2.2 ± 0.2 12.4 ± 0.7  Stillen 1.0 ± 0.4 1.8 ± 0.21.4 ± 0.2 3.0 ± 0.0 2.6 ± 0.2 9.8 ± 0.5 Mucosta 0.8 ± 0.4 0.8 ± 0.4 1.2± 0.2 2.4 ± 0.2 2.2 ± 0.2 7.4 ± 0.7 Momordicae 0.0 ± 0.0 0.6 ± 0.2 0.6 ±0.2 1.2 ± 0.2 1.2 ± 0.4 3.6 ± 0.2 semen extract

As seen in Table 4, the Momordicae semen extract of Preparative Example1 had superior effect in treating the damaged gastric mucosa.

Example 4 Protective Effect of Momordicae semen Extract Against theStomach Damage Induced by Diclofenac

Differently from Example 3, diclofenac and the test drug wereadministered simultaneously and the damage of gastric mucosa wasobserved 6 hours later. In order to prevent the direct interactionbetween diclofenac and the test drug, the test drug was administeredabdominally. Similar to that in Example 3, diclofenac and the test drugwere dissolved in 0.5% aqueous carboxymethyl cellulose solution to 10mg/mL.

Seven-week-old specific pathogen free (SPF) male Sprague-Dawley ratswere purchased from Charles River. After 1 week of adaptation, healthyrats with a weight of 220-225 g were selected for the test. Five ratsper each group were fasted for 18 hours with drinking water freelyavailable and diclofenac was orally administered at a dosage of 40 mg/kgand, at the same time, the test drug, or the Momordicae semen extract,and the control drugs Stillen and Mucosta were abdominally administeredat a dosage of 100 mg/kg. 6 hours later, the rats were anesthetized withether and the stomach was taken out in order to evaluate the drug'seffect of treating gastritis. The stomach was cut open along the greatercurvature and was observed with eyes. The damage of the stomach wasclassified into flare, congestion, hemorrhage, inflammation and edema.The severity of the damage was evaluated with points ranging from 0 to3.

TABLE 5 Damage of gastric mucosa (gastric mucosa damage index) CategoryFlare Hyperemia Bleeding Erosion Edema Total Water 2.2 ± 0.4 1.4 ± 0.22.4 ± 0.4 2.4 ± 0.4 2.0 ± 0.3 10.4 ± 1.4  Stillen 1.8 ± 0.5 0.8 ± 0.21.4 ± 0.2 1.8 ± 0.2 1.6 ± 0.2 7.4 ± 1.2 Mucosta 2.6 ± 0.2 2.2 ± 0.4 1.4± 0.5 2.4 ± 0.4 1.2 ± 0.2 9.8 ± 1.2 Momordicae 1.6 ± 0.4 0.8 ± 0.4 0.8 ±0.4 1.2 ± 0.2 1.4 ± 0.2 5.8 ± 1.4 semen extract

As seen in Table 5, the Momordicae semen extract had the effect oftreating the damaged gastric mucosa in addition to the capability ofreducing the damage of gastric mucosa induced by NSAIDs, whenadministered along with NSAIDs such as diclofenac.

Example 5 Protective Effect of Momordica Saponin I Against the StomachDamage Induced by Diclofenac

Diclofenac and the test drug were administered simultaneously and thedamage of gastric mucosa was observed 4 hours later. Diclofenac wasdissolved in 0.5% aqueous carboxymethyl cellulose solution to 40 mg/mLand the test drug was prepared as in Example 2.

Seven-week-old specific pathogen free (SPF) male Sprague-Dawley ratswere purchased from Charles River. After 1 week of adaptation, healthyrats with a weight of 220-225 g were selected for the test. Five ratsper each group were fasted for 18 hours with drinking water freelyavailable and diclofenac was orally administered at a dosage of 40 mg/kgand, at the same time, the test drug, or momordica saponin I, was orallyadministered at a dosage of 20 mg/kg and the control drug Mucosta wasorally administered at a dosage of 100 mg/kg. 4 hours later, the ratswere anesthetized with ether and the stomach was taken out in order toevaluate the drug's effect of treating gastritis. The stomach was cutopen along the greater curvature and was observed with eyes. The damageof the stomach was classified into flare, congestion, hemorrhage,inflammation and edema. The severity of the damage was evaluated withpoints ranging from 0 to 3 (The higher the point, the severer thedamage).

TABLE 6 Damage of gastric mucosa (gastric mucosa damage index ± standarddeviation) Category Flare Hyperemia Bleeding Erosion Edema Total Water  2 ± 0.3 1.5 ± 0.3 2.6 ± 0.3 2.8 ± 0.5 1.4 ± 0.2 10.3 ± 1.6  Mucosta2.3 ± 0.3 1.3 ± 0.4 1.5 ± 0.3 2.2 ± 0.4 1.2 ± 0.1 8.5 ± 1.5 Momordica1.3 ± 0.2 0.9 ± 0.3 0.7 ± 0.2 1.3 ± 0.3   1 ± 0.2 5.2 ± 1.2 saponin I

As seen in Table 6, momordica saponin I had the ability of reducing thedamage of gastric mucosa caused by NSAIDs such as diclofenac.

Example 6 Gastric Acid Secretion Inhibition Test for Momordica Saponin Iin Rats

Momordica saponin I was orally administered to Sprague-Dawley rats andthe acidity in the stomach was measured in order to evaluate the effectof momordica saponin I on the secretion of gastric acid. The momordicasaponin I isolated in Preparative Example 4 was dissolved in 0.5%aqueous carboxymethyl cellulose solution to concentrations of 0.5, 1.5and 4.5 mg/mL. 7-week-old specific pathogen free (SPF) maleSprague-Dawley rats were purchased from Charles River. After 1 week ofadaptation, healthy rats with a weight of 220-225 g were selected forthe test. Two rats per each group were fasted for 18 hours with drinkingwater freely available and momordica saponin I were administered atdosages of 5, 15 and 45 mg/kg. 1 hour later, the rats were anesthetizedwith ether. 0.5 mL of the gastric juice taken from the stomach wasdiluted 10 times with distilled water to obtain a 5 mL sample. The pH ofthe diluted gastric juice was measured with a pH meter.

TABLE 7 Acidity in the stomach of rats (pH ± standard deviation)Momordica saponin I Vehicle 5 mg/kg 15 mg/kg 45 mg/kg 2.3 ± 0.6 3.3 ±0.1 4.3 ± 0.8 5.2 ± 0.6

As seen in Table 7, momordica saponin I effectively reduced the acidityof the gastric juice and thus can be useful in treating gastritis orgastric ulcer.

Example 7 Acute Toxicity Test for Oral Administration of Momordicaesemen Extract in Rats

Acute toxicity test was performed as follows using 6-week-old specificpathogen free (SPF) Sprague-Dawley rats

To two rats per each group, the Momordicae semen extract prepared inPreparative Example 1 was orally administered once at a dosage of 1g/kg. Survival, clinical manifestations and body weight change wereobserved and hematological and serum biochemical analysis was performed.Autopsy was performed to observe abnormalities in abdominal and thoracicorgans. There was no noticeable clinical manifestation or death. Inaddition, no toxicity was found in body weight change, hematological andserum biochemical analysis and autopsy. The Momordicae semen extract ofthe present invention showed no toxicity in all rats up to the dosage of2,000 mg/kg and was proved to be a safe substance with a minimum oraladministration lethal dose (LD₅₀) of 2,000 mg/kg or larger.

Example 8 Acute Toxicity Test for Oral Administration of MomordicaSaponin I in Rats

Acute toxicity test was performed as follows using 6-week-old specificpathogen free (SPF) Sprague-Dawley rats

To two rats per each group, the momordica saponin I isolated inPreparative Example 5 was orally administered once at a dosage of 400mg/kg. Survival, clinical manifestations and body weight change wereobserved and hematological and serum biochemical analysis was performed.Autopsy was performed to observe abnormalities in abdominal and thoracicorgans. There was no noticeable clinical manifestation or death. Inaddition, no toxicity was found in body weight change, hematological andserum biochemical analysis and autopsy. The momordica saponin I of thepresent invention showed no toxicity in all rats up to the dosage of 400mg/kg and was proved to be a safe substance with a minimum oraladministration lethal dose (LD₅₀) of 400 mg/kg or larger.

Preparation Example 1 Preparation of Tablet Containing Momordicae semenExtract

The Momordicae semen extract of the present invention was prepared intotablet for oral administration by wet granulation and dry granulation.

[Composition]

Momordicae semen extract (200 mg), light anhydrous silica acid (10 mg),magnesium stearate (2 mg), microcrystalline cellulose (50 mg), sodiumstarch glycolate (25 mg), cornstarch (113 mg), anhydrous ethanol(adequate).

Preparation Example 2 Preparation of Tablet Containing Momordica SaponinI

The momordica saponin I of the present invention was prepared intotablet for oral administration by wet granulation and dry granulation.

[Composition]

Momordica saponin I (20 mg), light anhydrous silica acid (10 mg),magnesium stearate (2 mg), microcrystalline cellulose (50 mg), sodiumstarch glycolate (25 mg), cornstarch (113 mg), anhydrous ethanol(adequate).

Preparation Example 3 Preparation of Ointment Containing Momordicaesemen Extract

The Momordicae semen extract of the present invention was prepared intoointment.

[Composition]

Momordicae semen extract (5 g), cetyl palmitate (20 g), cetanol (40 g),stearyl alcohol (40 g), isopropyl myristate (80 g), sorbitanmonostearate (20 g), polysorbate (60 g), propyl p-hyroxybenzoate (1 g),methyl p-hyroxybenzoate (1 g), phosphoric acid and purified water(adequate).

Preparation Example 4 Preparation of Injection Containing Momordicaesemen Extract

The Momordicae semen extract of the present invention was prepared intoinjection.

[Composition]

Momordicae semen extract (100 mg), mannitol (180 mg), dibasic sodiumdiphospate (25 mg), water for injection (2974 mg)

Preparation Example 5 Preparation of Transdermal Agent ContainingMomordicae semen Extract

The Momordicae semen extract of the present invention was prepared intoa transdermal agent.

[Composition 1]

Momordicae semen extract (0.4 g), sodium polyacrylate (1.3 g), glycerin(3.6 g), aluminum hydroxide (0.04 g), methyl paraben (0.2 g), water (14g).

[Composition 2]

Momordicae semen extract (0.8 g), propylene glycol (1.6 g), liquidparaffin (0.8 g), isopropyl myristate (0.4 g), gelba 1430 (16.4 g).

Preparation Example 6 Preparation of Transdermal Agent ContainingMomordica Saponin I

The momordica saponin I of the present invention was prepared into atransdermal agent.

[Composition 1]

Momordica saponin 1 (20 mg), sodium polyacrylate (1.3 g), glycerin (3.6g), aluminum hydroxide (0.04 g), methyl paraben (0.2 g), water (14 g).

[Composition 2]

Momordica saponin I (40 mg), propylene glycol (1.6 g), liquid paraffin(0.8 g), isopropyl myristate (0.4 g), gel bar 1430 (16.4 g).

INDUSTRIAL APPLICABILITY

As apparent from the above description, the Momordicae semen extract inaccordance with the present invention and momordica saponin I isolatedtherefrom are very useful for the prevention and treatment of gastritisor gastric ulcer as they have superior effects in preventing the damageof gastric mucosa induced by alcohols and non-steroidalanti-inflammatory drugs (NSAID) and also inhibiting the secretion ofgastric acid.

Those skilled in the art will appreciate that the concepts and specificembodiments disclosed in the foregoing description may be readilyutilized as a basis for modifying or designing other embodiments foraccomplishing the same purposes of the present invention. Those skilledin the art will also appreciate that such equivalent embodiments do notdepart from the spirit and scope of the present invention according tothe appended claims.

1. A drug for the prevention and treatment of gastritis or gastric ulcercomprising a Momordicae semen extract as an active ingredient.
 2. Thedrug according to claim 1, wherein the Momordicae semen extract isobtained by extracting Momordicae semen with water or alcohol solution.3. The drug according to claim 2, wherein said alcohol is a C₁-C₆alcohol.
 4. A drug for the prevention and treatment of gastritis orgastric ulcer comprising the momordica saponin I represented by thefollowing formula (1) .

as an active ingredient.
 5. The drug according to claim 4 which contains0.05-1 mg of momordica saponin I per 1 kg of body weight.